predictive value of serum ifn inducible protein 10 and ifn il 4 ratio for liver fibrosis progression in chb patients

www.nature.com/scientificreports OPEN received: 19 July 2016 accepted: 06 December 2016 Published: 09 January 2017 Predictive Value of Serum IFN-γ inducible Protein-10 and IFN-γ/IL-4 Ratio for Liver Fibrosis Progression in CHB Patients Yadong Wang1, Weiyan Yu1, Chuan Shen1, Wei Wang1, Li Zhang1, Fang Liu1, Hui Sun1, Yajuan Zhao2, Honghao Che3 & Caiyan Zhao1 Noninvasive serum markers for assessment of liver fibrosis in chronic hepatitis B (CHB) patients have not been well-studied The present study was to evaluate the predictive value of serum interferon gamma-inducible protein-10 (IP-10/CXCL10) and the interferon (IFN)-γ/interleukin (IL)-4 ratio for liver fibrosis progression in CHB patients A total of 180 CHB patients were categorized into four groups: no fibrosis, mild fibrosis, moderate fibrosis, and severe fibrosis Serum and intrahepatic levels of IP10, IFN-γ, and IL-4 were examined, from which the IFN-γ/IL-4 ratio was calculated We found that the serum IP-10 levels were positively correlated with the severity of liver fibrosis, whereas the IFN-γ/ IL-4 ratio was negatively associated with the progression of hepatic fibrosis Multivariate logistic regression analysis revealed that the serum IP-10 was an independent predictor for significant fibrosis For predicting significant fibrosis, the IP-10 cut-off value of 300 ng/mL had a sensitivity of 92.7% and a specificity of 68.6% When the IP-10 level was combined with the IFN-γ/IL-4 ratio, the specificity and positive predictive value were 93.8% and 94.6%, respectively; thus, the discriminatory ability was much improved In conclusion, the serum IP-10 level and the IFN-γ/IL-4 ratio have great potential to predict significant fibrosis among CHB patients Chronic hepatitis B virus (HBV) infection is one of the major causes of serious liver diseases, including liver cirrhosis and hepatocellular carcinoma (HCC), through a complicated course with fibrosis as a middle essential stage1–3 Early detection, diagnosis, and appropriate medical intervention are important to slow down or even stop the rapid progression of HBV-related liver fibrosis into cirrhosis and HCC Liver biopsy has traditionally been considered as the gold standard for assessment of hepatic fibrosis in chronic hepatitis B (CHB) patients4, but it is an invasive procedure with several limitations such as sampling errors and intra- and inter-observer variability And this technique has recently been challenged by the development of several novel noninvasive tests, relying on quantification of serum markers of liver fibrosis, measurement of liver stiffness by imaging techniques, or the combination of these two approaches The last decade has witnessed the rapid progress in developing serum markers for the prediction and diagnosis of hepatic fibrosis, such as APRI Score, Fibro Test, FIB-4 index, Hui Score, Zeng Score, etc.5,6 However, most of the evaluations of serum markers have been performed in patients with chronic hepatitis C virus (HCV) infection, whereas there were only limited data on the serum markers for the early detection and diagnosis of HBV-related fibrosis A study of 284 of HBV patients and 913 of HCV patients was performed to evaluate diagnostic performance of FibroTest, Firbrometre, Hepacore, and APRI, the range of the area under the receiver operator characteristic curve (AUROC) values in predicting significant liver fibrosis were from 0.72 to 0.787 In the two noninvasive models, Hui Score8 and Zeng Score9, developed for prediction of significant fibrosis in CHB patients, the mean values of the AUROC in diagnosis of significant liver fibrosis were 0.79 and 0.77, respectively Obviously, the existing noninvasive models of the serum markers showed lower diagnostic performance for prediction of significant liver fibrosis in HBV patients Thus, novel noninvasive Department of Infectious Disease, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China 2Division of Liver Disease, The Infectious Disease Hospital of Handan City, Handan, Hebei, China 3Department of Gastroenterology and Hepatology, The First Hospital of Shijiazhuang City, Shijiazhuang, Hebei, China Correspondence and requests for materials should be addressed to C.Z (email: zhaocy2005@163.com) Scientific Reports | 7:40404 | DOI: 10.1038/srep40404 www.nature.com/scientificreports/ Characteristic F0 F1–2 F3–4 n 15 55 68 42 31 ±​  10 35 ±​  10 34 ±​  12 38 ±​  14 Mean age, years F5–6 Male/Female, n 7/8 28/27 36/32 24/18 WBC, ×​109/L 6.82 ±​  1.44 6.26 ±​  1.52 6.38 ±​  1.67 6.20 ±​  2.14 PLT, ×​109/L 224 ±​  43 159 ±​  45a 156 ±​  40a 127 ±​  33abc Albumin, g/L 42.61 ±​  4.20 40.69 ±​  4.81 40.81 ±​  4.82 37.61 ±​  4.16abc Serum ALT, U/L 49 ±​  23 97 ±​  38a 124 ±​  42ab 118 ±​  55ab Serum AST, U/L 47 ±​  18 83 ±​  33a 81 ±​  39a 93 ±​  38a Serum TBil, μ​M 15.57 ±​  4.29 15.94 ±​  5.23 18.52 ±​  5.94b 25.55 ±​  6.15abc PT, s 11.02 ±​  0.42 11.87 ±​  0.83a 12.17 ±​  0.90a 12.33 ±​  1.22a 133.10 ±​  17.20 114.52 ±​  16.24a 109.69 ±​  15.82a 100.83 ±​  15.69abc INR 0.82 ±​  0.09 0.93 ±​  0.12a 0.95 ±​  0.12a 1.05 ±​  0.15abc HBV DNA, Log10 cp/mL 6.32 ±​  0.36 6.11 ±​  0.89 5.85 ±​  1.02 5.96 ±​  0.80 12/3 35/20 35/33a 7325 ±​  2546 5102 ±​  2810 PTA, % HBeAg, +​  /−(n) Serum HBsAg, IU/mL a 18/24ab 5277 ±​  2957 a 2438 ±​  1776abc Table 1.  Characteristics of the 180 chronic hepatitis B patients with or without hepatic fibrosis WBC, white blood cell; PLT, platelets; ALT, alanine aminotransferase; AST, aspartate aminotransferase; TBil, serum total bilirubin; PT, prothrombin time; PTA, prothrombinase activity; INR, international normalized ratio; HBV, hepatitis B virus; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen aDiffers from the F0 group, P